不同处方工艺的复方醋酸地塞米松乳膏的裸鼠皮肤药动学行为比较  

Dermatopharmacokinetics of Different Formulation and Preparation of Dexamethasone Acetate Creams in Nude Mouse

作　　者：李玲珺[1] 马鹏程[1] 魏峻[1] 钱坤[1] 陶蕾 

机构地区：[1]中国医学科学院皮肤病研究所,南京210042

出　　处：《中国药学杂志》2015年第14期1228-1232,共5页Chinese Pharmaceutical Journal

基　　金：中央级公益性科研院所基本科研业务专项资助项目(2011PYS003);南京药学会-常州四药医院药学科研基金资助项目(2013YX013)

摘　　要：目的 利用裸鼠在体皮肤给药,比较3种不同处方工艺的醋酸地塞米松乳膏皮肤药动学行为,同时探讨裸鼠在体皮肤药动学方法的应用前景。方法 选择裸鼠背部皮肤在体涂复方醋酸地塞米松乳膏约0.025 g后,于0、0.25、0.75、1.75、3、5、8、12、24 h后去除残余药物,取皮,称重,甲醇匀浆沉淀蛋白,采用高效液相色谱-电喷雾离子质谱联用法（LC-ESI-MS）测定裸鼠皮肤中的醋酸地塞米松浓度,计算药动学参数,同时对三种乳膏裸鼠经皮吸收的行为进行评价。结果 该测定方法没有内源性物质干扰,醋酸地塞米松皮肤匀浆液浓度在0.052 4-5.24μg·mL^-1内,线性关系良好。3种浓度的回收率分别是95.97%、89.95%、91.72%,精密度的RSD均〈15%,样品的稳定性良好。经测定,处方中含二甲基亚砜（DMSO）能增加醋酸地塞米松的皮肤药动学参数AUC值,而乳膏粒度大、有结晶则减少醋酸地塞米松的皮肤药动学参数AUC值。结论 LC-ESIMS分析方法快速、灵敏、准确,回收率高,重现性好,检测限低,可成功的用于测定醋酸地塞米松在裸鼠皮肤中的浓度,较好地反映醋酸地塞米松在裸鼠皮肤中的经皮吸收行为,裸鼠在体给药分时取样法可用于临床前外用药物的皮肤药动学筛选与评价。OBJECTIVE To study the dermatopharmacokinetics of dexamethasone acetate by administering three different formulation and preparationcreams on skin of nude mouse and discuss the application prospect of the method. METHODS At 0,0. 25, 0.75, 1.75, 3, 5, 8, 12, 24 h after administered dexamethasone acetate cream about 0. 025 g on the back of the nude mice, the excess formulation was gently removed. Then mice were sacrificed at the chosen contact time points. Skin samples were immediately excised from the fixed area of skin and weighed. Both compounds were precipitated from skin homogenate with methanol. The concentrations of dexamethasone acetate in skin were analyzed by using LC-ESI-MS method. The pharmacokineties parameters were calculated and the percutaneous absorption process in skin of nude mouse was evaluated. RESULTS This determination method does not interfere with endogenous substances. Calibration curves were linear over the range of 0. 052 4 -5.24 μg·mL^-1. The mean recovery was in the ranges of 89.95% -95.97%. The intra-run relative standard deviations were less than 15%. All the results showed there were no stability related problems during the samples＇ routine analysis. DMSO can increase the AUC value of dexamethasone acetate, coarse granularity and crystal of cream may decrease the AUC value of dexamethasone acetate. CONCLUSION This method is fast, sensitive, accurate with good recovery, reproducibility and low detection limited, which can be successfully applied to determine the concentration of dexamethasone acetate in skin and study the dermatopharmacokinetics of nude mouse. This in vivo time-share sampling method can be used in preclinical evaluation and screening the of topical drugs.

关 键 词：醋酸地塞米松 乳膏 制剂处方 测定 皮肤 裸鼠 皮肤药动学 

分 类 号：R969.1[医药卫生—药理学]